A Novel Synthesis of Biscoumarin derivatives Catalyzed by Zncl₂ Under Solvent-Free Conditions

Introduction

Biscoumarin and its derivatives are of considerable interest due to their biological activities such as  urease inhibitors¹, HIV inhibitory activity ², anticoagulant activity ³, treatment of thrombosis ⁴. From among various catalyst for synthesis of  Biscoumarins, the following catalysts can be referred such as sulfuric acid, phosphorus pentoxide, aluminumchloride, iodine, and trifluoroacetic acid are employed ^5-6, molecular iodine ⁷, [bmim][BF₄] ⁸, tetrabutylammonium bromide (TBAB) ⁹, Zn(Proline)₂¹⁰, sodium dodecyl sulfate (SDS) ¹¹.Previously, we have synthesized a number of heterocyclic compounds^12-22. Herein, we report an efficient method for the synthesis of somebiscoumarin derivatives from aromatic aldehydes and 4-hydroxycoumarin catalyzed by Zinc chloride under solvent-free conditions (Scheme 1).

 

Scheme 1  Click here to View Scheme

 

EXPERIMENTAL

All chemicals were obtained from Merck or Flukawithout further purification. Silica gel SILG/UV 254 plates were used for TLC. IR spectra were measured on a Shimadzu IR-470 Spectrophotometer. ¹H NMR spectra were determined on Bruker400 DRX AVANCE instrument at 400 MHz, respectively.

General procedure for preparation of H1-H4

A mixture of aldehyde (1 mmol), 4-hydroxycoumarin (1 mmol), ammonium acetate (3 mmol) and ZnCl₂(15mol %) as a catalyst was stirred at 110 ^oC for 35 min. The progress of reaction was monitored by TLC. After finishing, recrystallized from ethanol 95% to give pure products (H1-H4)

spectral data

3,3′-[(3-Nitrophenyl)methylene]bis(4-hydroxy-2H-chromen-2-one) (H1)

White crystals, Yield: (89%), mp 233-235^oC. IR (ν_max/cm^-1) (VBr): 3120(arom. CH Str.); 1680,1630 (C=O Str.); 1540 , 1340 (NO₂ Str.) ; 1490(C=C Str.).¹H-NMR (400.13 MHz CDCl₃): δ=6.15(H, s, CH); 7.40-7.61(6H, m, 6CH); 7.69(2H, t,³J=7.6 Hz, 2CH); 8.03(H, d, ³J=7.6 Hz, CH); 8.09(H, s, CH); 8.12( H, t, ³J=7.6 Hz, CH); 8.17(H, d, ³J=8.0 Hz, CH); 11.40(H, s, OH); 11.60(H, s, OH).

3,3′-[(4-Nitrophenyl)methylene]bis(4-hydroxy-2H-chromen-2-one) (H2)

White crystals, Yield: (87%), mp230-232^oC.IR (ν_max/cm^-1) (VBr): 3140(arom. CH Str.); 1670,1610 (C=O Str.); 1580 , 1370 (NO₂ Str.) ; 1480(C=C Str.). ¹H-NMR (400.13 MHz CDCl₃): δ=6.13(H, s, CH); 7.41-7.47(6H, m, 6CH); 7.69(2H, t,³J=8.0 Hz, 2CH); 8.02(H, d, ³J=7.6 Hz, CH); 8.10(H, d, ³J=7.8 Hz CH); 8.20( 2H, d, ³J=8.8 Hz, 2CH); 11.39(H, s, OH); 11.59(H, s, OH).

3,3′-[(2-Chlorophenyl)methylene]bis(4-hydroxy-2H-chromen-2-one) (H3)

White crystals, Yield: (90%), mp225-223 ^oC.IR (ν_max/cm^-1) (VBr): 3120(arom. CH Str.); 1660, 1620 (C=O Str.); 1490(C=CStr.). ¹H-NMR (400.13 MHz CDCl₃): δ=6.16(H, s, CH); 7.24-7.39(5H, m, 5CH); 7.41(2H, d,³J=8.0 Hz, 2CH); 7.49(1H, d,³J=8.0 Hz, CH); 7.64(2H, t, ³J=7.6 Hz, 2CH); 8.04(2H, m,2CH); 10.95(H, s, OH); 11.67(H, s, OH).

3,3′-[(2-Fluorophenyl)methylene]bis(4-hydroxy-2H-chromen-2-one) (H4)

White crystals, Yield: (85%), mp 215-217^oC. IR (ν_max/cm^-1) (VBr): 3130(arom. CH Str.); 1675, 1605 (C=O Str.); 1510(C=C Str.). ¹H-NMR (400.13 MHz CDCl₃): δ=6.13(H, s, CH); 7.18-7.37(8H, m, 8CH); 7.43(1H, d,³J=8.2 Hz, CH); 7.65(2H, d,³J=8.2 Hz, 2CH); 8.03(2H, dd, ³J=28.0 Hz, ³J=8.0 Hz, 2CH); 11.33(H, s, OH); 11.56(H, s, OH).

RESULTS AND DISCUSSION

We have been able to introduce an efficient method for the synthesis of biscoumarin derivatives via condensation of 4-hydroxycoumarin with various aromatic aldehydes. Therefore, reported ZnCl₂as catalyst which could provide an efficient, cheap, easy separationunder solvent-free condition for the synthesis of biscoumarins with high yield.

ACKNOWLEDGEMENTS

We gratefully acknowledge the financial support from the Research Council of Tonekabon Branch Islamic Azad University.

REFERENCES

1. Khan K.M., Iqbal S., Lodhi M.A. and et al., Bioorg. Med. Chem.,12: 1963 (2004).
2. Manian R.D.R.S., JayashankaranJ.andRaghunathan R., Tetrahedron Lett.,48: 1385 (2007).
3. Manolov I., Moessmer C.M., Nicolova I. and Danchev N., Arch. Pharm. Chem. Life Sci., 339: 319 (2006).
4. Lehmann J., Lancet, 241: 611 (1943).
5. Yadav J.S., Reddy B.V.S., Basak A.K. and et al., Eur. J. Org. Chem., 546 (2004).
6. Narsaiah A.V. andNagaiah K., Synth. Commun.,21:3825 (2003).
7. Kidwai M., Bansal V., Mothsra P. and et al., J. Mol. Catal. A: Chem.,268:76 (2007).
8. Khurana J.M. and Kumar S., Monatsh. Chem.,141:561 (2010).
9. Khurana J.M. and Kumar S., Tetrahedron Lett.,50: 4125 (2009).
10. Siddiqui Z. andFarooq F., Catal. Sci. Technol.,1:810 (2011).
11. Mehrabi H. andAbusaidi H., J. Iran Chem. Soc.,7:890 (2010).
12. Azizian J., Hatamjafari F., Karimi A. R. and Shaabanzadeh M., Synthesis. 5: 765 (2006).
13. Azizian J., Shaabanzadeh M., Hatamjafari F. and Mohammadizadeh M.R., Arkivoc. (xi): 47 (2006).
14. Hatamjafari F., Synthetic Communications. 36: 3563 (2006).
15. Azizian J., Hatamjafari F. and Karimi A. R., Journal of Heterocyclic Chemistry. 43: 1349 (2006).
16. Hatamjafari F and Montazeri N., Turkish Journal of Chemistry. 33: 797 (2009).
17. Hatamjafari F., Orient. J. Chem., 28: 141(2012).
18. Hatamjafari F., Orient. J. Chem., 29: 93(2013).
19. Hatamjafari F and Alijanichakoli F., Orient. J.Chem.,29: 145(2013).
20. Hatamjafari F and Hosseinian A., Orient. J.Chem.,29: 109(2013).
21. Hatamjafari F and Khojastehkouhi H., Orient. J. Chem., 30: (2014 in press).
22. Hatamjafari F and GermaniNezhad F., Orient. J. Chem., 30: (2014 in press).

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